An Adenovirus-Vectored Nasal Vaccine Confers Rapid and Sustained Protection against Anthrax in a Single-Dose Regimen

Zhang, Jianfeng; Jex, Edward; Feng, Tsungwei; Sivko, Gloria S.; Baillie, Les; Goldman, Stanley; Kampen, Kent R. Van; Tang, De-chu C.

doi:10.1128/cvi.00280-12

Cited by 25 publications

(17 citation statements)

References 44 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Intranasal vaccination with AdVAV was well tolerated in this study, consistent with previous data obtained in mice (10). Replication-deficient adenoviral vectors have been extensively studied as vehicles for gene therapy and vaccine delivery.…”

Section: Discussionsupporting

confidence: 90%

“…The duration of the immune response is a hallmark of AdVAV vaccine activity. When a single intranasal dose of AdVAV was used to vaccinate A/J mice, anti-PA IgG ELISA titers in the vaccinated mice were maintained at the 1-month postvaccination level for at least 1 year (10).…”

Section: Discussionmentioning

confidence: 99%

“…Frequently, one or more of the E3 gene products are also deleted in order to abolish the immunosuppressive activities of some E3 gene products (9) and to allow for insertion of larger or multiple transgenes. As vaccines, adenoviral expression vectors possess distinct advantages compared to protein-based vaccines, including intracellular expression of the immunogen leading to induction of robust cellular and humoral immunity, the ability to administer the vaccine through a variety of routes, including intranasal (10,11), topical (12), oral (13), and traditional intramuscular routes (14,15), and improved vaccine stability profiles. Intranasal administration of adenoviral-vectored vaccines is a simple, noninvasive method of vaccination that also has the potential to induce mucosal immunity at the site of vaccination to provide first-line defense against pathogens that enter the body through the respiratory tract (11,16,17).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Efficacy and Immunogenicity of Single-Dose AdVAV Intranasal Anthrax Vaccine Compared to Anthrax Vaccine Absorbed in an Aerosolized Spore Rabbit Challenge Model

Krishnan¹,

Andersen²,

Shoemaker³

et al. 2015

Clin. Vaccine Immunol.

Self Cite

View full text Add to dashboard Cite

cAdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 ؋ 10 7 , 1.5 ؋ 10 9 , or 3.5 ؋ 10 10 viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 ؋ 10 10 viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD 50 ) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. Bacillus anthracis is a Gram-positive, rod-shaped, spore-forming bacterial pathogen and is the etiological agent of anthrax disease. Inhalation of the B. anthracis spores is associated with high levels of mortality in exposed individuals and has led to the use of aerosolized B. anthracis spores as a bioterror weapon (1-3). Following spore inhalation, B. anthracis undergoes a transformation from quiescent spores into a vegetative state associated with active growth and release of two binary toxins that mediate the majority of the pathological effects of anthrax disease. These toxins, lethal toxin and edema toxin, are formed through the interaction of lethal factor (LF) and edema factor (EF) with protective antigen (PA) (4). Vaccines against anthrax are not intended to inhibit B. anthracis vegetative growth but rather are directed against PA and the central role this protein plays in the pathogenesis of anthrax disease. Previous studies have shown that neutralizing antibody to PA is correlated with protection from anthrax disease (5-8).Vaccines derived from replication-deficient adenoviral vectors are deleted in E1 gene function, ensuring that replication can only be supported in specialized cell lines that provide the essential E1 function in trans. Frequently, one or more of the E3 gene products are also deleted in order to abolish the immunosuppressive activities of some E3 ge...

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Efficacy and Immunogenicity of Single-Dose AdVAV Intranasal Anthrax Vaccine Compared to Anthrax Vaccine Absorbed in an Aerosolized Spore Rabbit Challenge Model

Krishnan¹,

Andersen²,

Shoemaker³

et al. 2015

Clin. Vaccine Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, a number of studies indicated that administration of Ad5-vectored vaccines via the i.n. route might overcome preexisting immunity against the Ad5 vector (72)(73)(74)(75). We did observe slightly lower Y. pestis antigen-specific antibody titers in mice with the preexisting adenoviral immunity than in those animals without the preexisting adenoviral immunity when mice were i.n.…”

Section: Discussionmentioning

confidence: 55%

A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates

Sha

Kirtley

Klages

et al. 2016

Clin Vaccine Immunol

View full text Add to dashboard Cite

j Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis. We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models. Yersinia pestis is the causative agent of plague and can be transmitted to humans via an infected flea bite or by direct inhalation of the aerosolized bacilli from an infected person or an animal (1, 2). Plague manifests itself in three major forms in humans, namely, bubonic, septicemic, and pneumonic (2). Pneumonic plague is the most feared form due to its rapid onset and associated high mortality rate (1, 2). Y. pestis has been responsible for at least three pandemics in the past, which killed more than 200 million people (3). Current epidemiological records suggest that there are 4,000 human plague cases annually worldwide (2). The emergence of multi-antibiotic-resistant Y. pestis strains from plague patients and the potential of malicious dissemination of recombinantly engineered bacteria as an airborne bioweapon necessitate the development of an effective preexposure and/or postexposure prophylaxis treatment (1, 2).Currently, no Food and Drug Administration (FDA)-licensed plague vaccine exists in the United States, and recent efforts have focused on the development of recombinant subunit plague vaccines consisting of two well-characterized Y. pestis antigens, the F1 capsular antigen and the type 3 secretion system (T3SS) component and effector LcrV (4-8). F1, encoded by the caf1 gene, has a polymeric structure and confers bacterial resistance to phagocytosis (9). The F1-V-based vaccines are generally protective ag...

show abstract

“…After that, the Ad vector expressing the B. anthracis PA domain 4 was developed for security reasons (32), and the primeboost vaccination strategy was also studied (33). Recently, Zhang et al (34) proved that an adenovirus-vectored nasal vaccine conferred rapid and sustained protection against anthrax in a singledose regimen. However, intramuscular inoculation with Ad5-PAopt in our work induced a faster immune response than intranasal route did in Zhang's work, even in the presence of PEI.…”

Section: Discussionmentioning

confidence: 99%

Intramuscular Delivery of Adenovirus Serotype 5 Vector Expressing Humanized Protective Antigen Induces Rapid Protection against Anthrax That May Bypass Intranasally Originated Preexisting Adenovirus Immunity

Zhang

et al. 2013

Clin. Vaccine Immunol.

View full text Add to dashboard Cite

Developing an effective anthrax vaccine that can induce a rapid and sustained immune response is a priority for the prevention of bioterrorism-associated anthrax infection. Here, we developed a recombinant replication-deficient adenovirus serotype 5-based vaccine expressing the humanized protective antigen (Ad5-PAopt). A single intramuscular injection of Ad5-PAopt resulted in rapid and robust humoral and cellular immune responses in Fisher 344 rats. Animals intramuscularly inoculated with a single dose of 10 8 infectious units of Ad5-PAopt achieved 100% protection from challenge with 10 times the 50% lethal dose (LD 50 ) of anthrax lethal toxin 7 days after vaccination. Although preexisting intranasally induced immunity to Ad5 slightly weakened the humoral and cellular immune responses to Ad5-PAopt via intramuscular inoculation, 100% protection was achieved 15 days after vaccination in Fisher 344 rats. The protective efficacy conferred by intramuscular vaccination in the presence of preexisting intranasally induced immunity was significantly better than that of intranasal delivery of Ad5-PAopt and intramuscular injection with recombinant PA and aluminum adjuvant without preexisting immunity. As natural Ad5 infection often occurs via the mucosal route, the work here largely illuminates that intramuscular inoculation with Ad5-PAopt can overcome the negative effects of immunity induced by prior adenovirus infection and represents an efficient approach for protecting against emerging anthrax.

show abstract

An Adenovirus-Vectored Nasal Vaccine Confers Rapid and Sustained Protection against Anthrax in a Single-Dose Regimen

Cited by 25 publications

References 44 publications

Efficacy and Immunogenicity of Single-Dose AdVAV Intranasal Anthrax Vaccine Compared to Anthrax Vaccine Absorbed in an Aerosolized Spore Rabbit Challenge Model

Efficacy and Immunogenicity of Single-Dose AdVAV Intranasal Anthrax Vaccine Compared to Anthrax Vaccine Absorbed in an Aerosolized Spore Rabbit Challenge Model

A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates

Intramuscular Delivery of Adenovirus Serotype 5 Vector Expressing Humanized Protective Antigen Induces Rapid Protection against Anthrax That May Bypass Intranasally Originated Preexisting Adenovirus Immunity

Contact Info

Product

Resources

About